Hypothesis / aims of study
Post-radical prostatectomy urinary incontinence (PPI) is a frequent and feared complication for urologists and patients. Between 1 and 10% of patients suffering from PPI will require surgical treatment. Several factors related to the patients and the devices have to be considered when choosing between the different surgical treatments for PPI. Benefits and harms of the different available surgical interventions have yet to be studied in a large and high quality randomised controlled trial (RCT). In addition, the available reviews have significant limitations regarding eligibility criteria, methodology and choice of outcomes. For example, a systematic review and meta-analysis from Chen et al. restricted its inclusion criteria to prospective studies and failed to provide data on adverse events. Recent systematic reviews from Radadia et al., Kretschmer et al. and Crivellaro et al. provided summary of evidence without pooled estimates, risk of bias assessments, publication bias assessments and evaluation of the quality of evidence[2,3]. However, they also neglected to evaluate subjective outcomes such as the impact on quality of life and patient’s impression of improvement. The absence of a strong summary of the evidence creates a real challenge for clinicians and patients in making an informed decision regarding the choice of the adequate intervention.
Our aim is to present systematic summaries of benefits and harms of contemporary surgical treatment options for PPI through systematic review and meta-analysis.
Study design, materials and methods
A systematic literature search of the OVID and PubMED platforms in the MEDLINE, Embase and Cochrane databases, and reference lists of relevant reviews and guidelines was performed from January 1st, 1997, to September 3rd, 2018. Studies pertaining to bulking agents, male synthetic slings, compressive balloon systems (ProACT) and/or artificial urinary sphincters (AUS) used for the treatment of patients suffering from PPI were considered. To be included, these studies had to include at least 50 participants and had to study at least one of our outcomes. Independent trained reviewers performed study selection, data extraction and risk of bias assessment. Our two primary outcomes for benefits and harms were the cure rate using the number of pads per day and the reoperation rates. Principal secondary outcomes were the major Clavien-Dindo complications (3 to 5), the change on the Incontinence - Quality of Life questionnaire (IQOL) and on the Patient Global Impression of Improvement (PGI-I).
The main analyses considered the data acquired the closest to 12 months. Two risks of bias instruments were used in the assessment: the CLARITY tool for observational studies and a new specific instrument which we created for the before-after study design with no control group. Pooled analysis of dichotomous and continuous outcomes were performed for each intervention using a random effects model including data acquired with less than 20% loss at the follow-up. Forest plots were created to illustrate the most important outcomes. Descriptive statistics were evaluated for study and patient’s characteristics. Publication bias was evaluated for outcomes including more than 10 studies using the Egger method for asymmetry from funnel plots. We assessed quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and created evidence profiles. Our methods were defined in a study protocol registered at PROSPERO CRD42018073923. Reporting is consistent with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA).
A total of 2737 articles were identified and 85 were included for analysis; 3 for bulking agents, 35 for slings, 10 for ProACT and 37 for AUS, involving 13 100 patients.
Data quality was evaluated for the body of evidence for each intervention and for each of our outcomes separately using GRADE. Bulking agents’ studies provided very low quality evidence for all outcomes. Very low and low quality data was assessed for ProACT. For slings and AUS, very low to moderate evidence was found. No assessments were of high quality. Quality of evidence for our primary outcomes is presented in tables 1 and 2.
The cure rates at 12 months using the number of pads per day were of 26.1% (95% CI 10.6-51.4) for the bulking agents based on 2 studies that included 384 patients; 58.6% (95% CI 51.3-65.5) for the slings based on 20 studies that included 1956 patients; 63.2% (95% CI 57.6-68.5) for the ProACT based on 6 studies that included 406 patients; and 74.0% (95% CI 61.2-83.7) for the AUS based on 9 studies that included 817 patients. The rates of reoperations at 12 months were of 5.0% (95% CI 2.4-9.8) for the slings based on 16 studies that included 1865 patients; 23.8% (95% CI 5.9-31.0) for the ProACT based on 3 studies that included 259 patients; and 22.2% (95% CI 15.2-31.3) for the AUS based on 12 studies that included 1596 patients. No studies reported data on reoperation rates following bulking agents. The rates of major Clavien-Dindo complications were of 2.8% (95% CI 1.2-5.4) for the slings based on 12 studies that included 1439 patients; 2.3% (95% CI 0.5-6.5) for the ProACT based on 1 studies that included 132 patients; and 9.0% (95% CI 4.9-15.9) for the AUS based on 10 studies that included 1486 patients. No data was available for Clavien-Dindo adverse events for bulking agents. The Incontinence – Quality of Life (IQOL) questionnaire score was increased by 32.2 points (95% CI 27.9-36.4) with slings based on 2 studies that included 198 patients. For ProACT, the score was increased by 35.4 points (95% CI 18.7-52.1) based on 3 studies that included 157 patients. The Patient Impression of Improvement (PGI-I) score was evaluated in 5 slings studies that included 690 patients and was of 1.6 (95% CI 1.3-1.8). None of the included studies reported subjective outcomes using IQOL or PGI-I for both the bulking agents and AUS.
Interpretation of results
Through this review, we have identified two major limitations in the management of PPI. First, the quality of the available studies to evaluate benefits of treatments for PPI is quite limited. Indeed, no RCTs were found to fit the eligibility criteria and the included observational studies were often of poor quality. In particular, the predominance of before-after study design without a control group or randomisation renders the field susceptible to biased interpretation. Regarding harms, quality of the evidence was found to be higher than for benefits, but the data remained limited by loss to follow-up and risk of selective reporting. Second, we believe that the estimates of effect of harms summarised in this paper are the best possible from the data available. However, this calls into question the rigor with which devices for PPI are evaluated prior to clinical use.